oral argument not yet scheduled nos. 15-5021, … · gas & elec. co. v. nat. res. def. council,...
TRANSCRIPT
ORAL ARGUMENT NOT YET SCHEDULED
Nos. 15-5021, 15-5022
United States Court of Appealsfor the District of Columbia Circuit
TAKEDA PHARMACEUTICALS U.S.A., INC., et al.
Plaintiffs-Appellants,
v.
SYLVIA MATHEWS BURWELL, in her official capacity asSECRETARY, UNITED STATES DEPARTMENT OF
HEALTH AND HUMAN SERVICES, et al.,
Defendants-Appellees,
and
HIKMA PHARMACEUTICALS PLC, et al.,
Intervenors-Defendants
On Appeal from the United States District Court for the District of Columbia,Docket No. 1:14-cv-1850 (K. Jackson, J.)
BRIEF OF AMICUS CURIAE GENERIC PHARMACEUTICALASSOCIATION IN SUPPORT OF APPELLEES AND INTERVENOR-
APPELLEES
Carlos T. AnguloAndrew N. GoldfarbZuckerman Spaeder LLP1800 M Street, NW, Suite 1000Washington, DC 20036Telephone: (202) [email protected]
October 23, 2015 Attorneys for Amicus CuriaeGeneric Pharmaceutical Association
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TABLE OF CONTENTS
Page
TABLE OF CONTENTS........................................................................................... i
CORPORATE AND FINANCIAL DISCLOSURE STATEMENT........................ ii
TABLE OF AUTHORITIES ................................................................................... iii
GLOSSARY...............................................................................................................v
CERTIFICATE OF PARTIES, RULINGS UNDER REVIEW, ANDRELATED CASES....................................................................................................v
STATUTES AND REGULATIONS.........................................................................v
STATEMENT OF IDENTITY AND INTEREST OF AMICUSCURIAE......................................................................................................................1
SUMMARY OF ARGUMENT .................................................................................2
ARGUMENT .............................................................................................................7
I. Takeda’s “most similar” test for listed drugs conflicts with thestatutory text and FDA’s consistent interpretation of section505(b)(2). .........................................................................................................7
A. Section 505(b)(2) gives the applicant the responsibility toselect the listed drug. .............................................................................7
B. The Court should preserve the intentional distinctions, inHatch-Waxman and in FDA’s administration of that law,between listed drugs for 505(b)(2) applications and RLDsfor ANDAs. .........................................................................................11
II. Elliott’s argument requiring a 505(b)(2) applicant to certify toall use patents covering the same use of the proposed drugwould fundamentally distort the Hatch-Waxman framework for505(b)(2) products. ........................................................................................14
III. Hatch-Waxman’s “grand bargain” does not support Appellants’statutory interpretations. ................................................................................17
CONCLUSION........................................................................................................18
CERTIFICATE OF COMPLIANCE.......................................................................20
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CORPORATE AND FINANCIAL DISCLOSURE STATEMENTPURSUANT TO FEDERAL RULES OF APPELLATE PROCEDURE 26.1
AND 29(c) AND D.C. CIRCUIT LOCAL RULE 26.1
Amicus curiae Generic Pharmaceutical Association (“GPhA”) is a trade
association with no parent corporation. No publicly held corporation has a 10% or
greater ownership interest in GPhA.
/s/ Carlos T. AnguloCarlos T. AnguloAndrew N. GoldfarbZuckerman Spaeder LLP1800 M Street, NW, Suite 1000Washington, DC 20036Telephone: (202) [email protected]
Attorneys for Amicus CuriaeGeneric Pharmaceutical Association
October 23, 2015
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TABLE OF AUTHORITIES
Page(s)
CASES
Balt. Gas & Elec. Co. v. Nat. Res. Def. Council, Inc.,462 U.S. 87 (1983) ...............................................................................................11
Chevron U.S.A., Inc. v. Nat. Res. Def. Council, Inc.,467 U.S. 837 (1984) .............................................................................................15
Hi-Tech Pharmacal Co. v. FDA,587 F. Supp. 2d 1 (D.D.C. 2008) .........................................................................14
Serono Labs., Inc. v. Shalala,158 F.3d 1313 (D.C. Cir. 1998) ...........................................................................11
Takeda Pharms. U.S.A., Inc. v. West-Ward Pharm. Corp.,785 F.3d 625 (Fed. Cir. 2015) ..............................................................................18
Teva Pharms. USA, Inc. v. Sebelius,595 F.3d 1303 (D.C. Cir. 2010) ...........................................................................14
STATUTES
*21 U.S.C. § 355(b)(2)...........................................................................................2, 7
21 U.S.C. § 355(c)(3)(C) ...........................................................................................4
21 U.S.C. § 355(c)(3)(E)(iii)............................................................................. 14, 18
21 U.S.C. § 355(j) ....................................................................................................11
21 U.S.C. § 355(j)(2)(A)..........................................................................................12
21 U.S.C. § 355(j)(2)(A)(iv) ....................................................................................12
21 U.S.C. § 355(j)(2)(C) ..........................................................................................12
21 U.S.C. § 355(j)(2)(C)(i) ......................................................................................12
*Authorities upon which we chiefly rely are marked with an asterisk.
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21 U.S.C. § 355(j)(5)(B)(IV) ...................................................................................14
OTHER AUTHORITIES
Consolidated Citizen Petition Response from Janet Woodcock toKatherine M. Sanzo, et al., at 6, Docket Nos. 2001P-0323/CP1 & C5,2002P-0447/CP1, and 2203P-0408/CP1 (Oct. 14, 2003) ..................................8, 9
FDA, Orange Book, http://tinyurl.com/65wqgnt.....................................................12
REGULATIONS
21 C.F.R. § 314.101(d)(9) (2014) ............................................................................12
21 C.F.R. § 314.94(a)(3) (2014) ..............................................................................12
21 C.F.R. § 320.1(c) (2014).....................................................................................13
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GLOSSARY
ANDA Abbreviated New Drug Application
FDA U.S. Food and Drug Administration
FDCA Federal Food, Drug and Cosmetic Act
JA Joint Appendix
RLD Reference Listed Drug
CERTIFICATE OF PARTIES, RULINGS UNDER REVIEW, ANDRELATED CASES
The parties in this case and the ruling under review are set forth in the
opening briefs for the Appellants.
STATUTES AND REGULATIONS
All applicable statutes and regulations are contained in the opening briefs for
the Appellants.
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STATEMENT OF IDENTITY AND INTEREST OF AMICUS CURIAE1
The Generic Pharmaceutical Association (“GPhA”) is a nonprofit, voluntary
association representing nearly 100 manufacturers and distributors of finished
generic pharmaceutical products, manufacturers and distributors of bulk active
pharmaceutical ingredients, and suppliers of other goods and services to the
generic pharmaceutical industry. GPhA’s core mission is to improve the lives of
consumers by providing timely access to affordable pharmaceuticals. GPhA’s
members provide American consumers with generic drugs that are just as safe and
effective as their brand-name counterparts, but substantially less expensive.
Generic medicines account for roughly 86% of all prescriptions dispensed in the
United States, but only 27% of the money spent on prescriptions. In this way, the
products sold by GPhA members save consumers more than $200 billion each
year. GPhA regularly participates in litigation as amicus curiae, taking legal
positions that are adopted by GPhA’s Board of Directors and that reflect the
position of GPhA as an organization.
GPhA has a strong interest in the proper interpretation of the drug approval
framework established by Congress in the “Hatch-Waxman” amendments to the
1 No party’s counsel authored this brief in whole or in part. No party or a party’scounsel made a monetary contribution intended to fund the preparation orsubmission of this brief, and no person other than amicus curiae, its members, orits counsel made such a monetary contribution. All parties have consented to thefiling of this amicus brief.
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Federal Food, Drug, and Cosmetic Act (“FDCA”). In particular, GPhA has an
overriding interest in ensuring that Hatch-Waxman is not interpreted to impose
barriers to competition in pharmaceutical markets, or to reduce patients’ access to
safe, effective, and affordable medicines, in ways that Congress did not intend.
This case involves the Hatch-Waxman “505(b)(2)” drug approval pathway
(21 U.S.C. § 355(b)(2)). The district court correctly upheld FDA’s interpretation
of section 505(b)(2) to allow the marketing of Intervenor-Appellees’ (hereafter
“Hikma”) anti-gout product Mitigare. The contrary readings of the statute urged
by Appellants unsuccessfully below and now on appeal are inconsistent with the
clear statutory language and with FDA’s longstanding interpretation of section
505(b)(2). If sustained by this Court, Appellants’ groundless interpretation of those
provisions would undermine the basic pro-competition and pro-access goals of
Hatch-Waxman.
SUMMARY OF ARGUMENT
FDA’s approval of Hikma’s colchicine anti-gout product Mitigare under
section 505(b)(2) of the FDCA followed FDA’s longstanding approach to that
pathway to market. Instead of undertaking costly, duplicative studies to establish
the safety and effectiveness of colchicine—an inexpensive drug that has been used
to treat gout for centuries—Hikma relied on FDA’s previous approval of a related,
approved colchicine-probenecid combination drug product, Col-Probenecid.
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Hikma supplemented that preexisting approval with its own studies of certain drug-
drug interactions relating to colchicine. Based on this combined information, FDA
determined that Mitigare was safe and effective and in 2014 approved Hikma’s
application, increasing price competition in the market for colchicine products.
This is exactly how section 505(b)(2) is supposed to work: as an accelerated path
to market for drug products that differ from previously approved products, giving
patients new therapies and increasing price competition.
In 2009, Appellant Takeda had, like Hikma, used the 505(b)(2) pathway to
obtain approval for its colchicine product, Colcrys®; and like Mitigare, Takeda
relied on a colchicine-probenecid combination product as its listed drug. Granted
exclusive marketing rights for single-ingredient colchicine for three years, Takeda
increased the price of the drug 50-fold. Appellants now contend that FDA’s
approval of Mitigare was illegal and seek to have it rescinded. Their goal is clear:
to reinstate Takeda’s monopoly in the colchicine product market and avoid genuine
price competition in that market for as long as possible. Appellants’ various
arguments largely boil down to the view that Hikma should have had to identify
Colcrys as its listed drug and therefore certify to Takeda’s patents for Colcrys.
Appellants complain that Hikma avoided patent certification obligations by relying
on Col-Probenecid, which is not patent-protected, as its listed drug. Under Hatch-
Waxman, if Hikma had been required to certify to the Colcrys patents, Takeda
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could have initiated patent litigation that would have delayed FDA’s approval of
Mitigare by up to 30 months and thereby delayed price competition in the market
for colchicine products. 21 U.S.C. § 355(c)(3)(C).
This brief addresses two distinct statutory arguments that Appellants, in their
attempt to force Mitigare off the market unless and until Hikma certifies to the
Colcrys patents, made unsuccessfully in the District Court and press again on
appeal.2
First, Appellant Takeda argues that FDA must require, and historically has
required, that a 505(b)(2) applicant identify as its listed drug, and therefore certify
to patents claiming, the approved drug “most similar” to its test product. Takeda
claims that, in the case of Mitigare, the “most similar” drug was Colcrys. Takeda
Br. 19-21. But as the district court correctly concluded (JA47-72), FDA has never
adopted Takeda’s “most similar” test. The inflexible standard Takeda seeks
conflicts with the text of section 505(b)(2) and FDA’s consistent interpretation that
it is the responsibility of the 505(b)(2) applicant to determine which listed drug to
2 GPhA does not address certain of Appellants’ other arguments, other than toagree with Appellees and Intervenor-Appellees that these arguments, which werealso uniformly rejected by the district court, are baseless. For example, GPhAdoes not address Appellants’ argument that FDA’s reliance on data as part of the505(b)(2) approval process, not just the applicant’s reliance in its application,triggers certification requirements. This argument was correctly rejected by thedistrict court (JA55-63), and in any event the district court also correctly concludedthat FDA in fact did not rely on Colcrys data to approve Mitigare (JA63-66). Nordoes GPhA address Appellants’ argument, also rejected below (JA85-93), thatFDA improperly approved the label for Mitigare.
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reference and how best to combine FDA’s prior approval of the listed drug with
new studies to secure a determination of safety and effectiveness from the agency.
By congressional design, the 505(b)(2) approach for listed drugs differs from the
more defined and narrow “reference listed drug” (“RLD”) requirements for
abbreviated new drug applications (“ANDAs”) for generic copies of branded drug
products under FDCA section 505(j). Takeda and its amicus the Pharmaceutical
Research and Manufacturers of America (“PhRMA”) seek to impose a parallel
RLD requirement for 505(b)(2) products that ignores these differences.
Second, Appellant Elliott argues that whether or not Colcrys was required to
be the listed drug for Mitigare, Hikma was required to certify to the Colcrys use
patents because a 505(b)(2) applicant is required to certify to any patents that claim
the same use as the test product, including use patents for drug products other than
the listed drug. Elliott Br. 16-21. PhRMA’s amicus brief varies this argument
slightly to claim that a 505(b)(2) applicant must certify to any patent for a product
that is “essential” to the test product’s approval, whether or not the patent was for
the listed drug. PhRMA Br. 23-25. Both these interpretations conflict with the
clear language of Hatch-Waxman (and FDA’s consistent interpretation of that
language), which requires a 505(b)(2) applicant to certify only to patents claimed
for a listed drug and none other. Elliott’s and PhRMA’s interpretations
fundamentally distort the basic Hatch-Waxman quid pro quo. The statute requires
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an applicant to certify to patents for a listed drug product as a price for being able
to rely on FDA’s prior approval of that same product. Elliott’s and PhRMA’s
readings would grant brand companies windfall opportunities to delay competition
through litigation on patents claimed for products that were not actually relied on
by the 505(b)(2) applicant.
Both of Appellants’ statutory arguments, if accepted, would have far-
reaching implications for 505(b)(2) products by expanding an applicant’s
certification obligations—and, therefore, the ability of brand companies to delay
competition from 505(b)(2) products through patent litigation—well beyond the
parameters established by Congress and applied by FDA. The district court
rejected Appellants’ construction of the FDCA and FDA regulations, and so too
should this Court.
While Appellants and PhRMA claim that their readings of Hatch-Waxman
are necessary to effectuate the “grand bargain” struck by Congress between
increasing competition and incentivizing innovation, these readings would in fact
skew that balance, by expanding patent certification obligations well beyond what
Congress expressly included and intended in Hatch-Waxman. Appellants’ bid to
impose these requirements in this case—where Takeda (1) itself used the very
same 505(b)(2) approval process that it now seeks to deny Hikma; and (2) has
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already pursued litigation against Hikma over Colcrys patents and lost—is
particularly misplaced.
ARGUMENT
I. Takeda’s “most similar” test for listed drugs conflicts with the statutorytext and FDA’s consistent interpretation of section 505(b)(2).
Takeda contends that FDA has historically required a 505(b)(2) applicant to
use as its listed drug the product “most similar” to the test product, and that
therefore Hikma should have been required to choose Colcrys as the listed drug for
its 505(b)(2) application for Mitigare. The district court correctly concluded that
Takeda’s argument “hinges on the existence of an FDA drug reference policy that
does not exist” (JA67), rejecting Takeda’s efforts to cobble together a supportive
agency position out of unrelated FDA statements that Takeda mischaracterizes or
takes out of context. JA67-72.
A. Section 505(b)(2) gives the applicant the responsibility to selectthe listed drug.
Section 505(b)(2) authorizes a manufacturer to submit for FDA approval an
application “for a drug for which the investigations . . . relied upon by the
applicant for approval . . . were not conducted by or for the applicant and for
which the applicant has not obtained a right of reference or use from the person by
or for whom the investigations were conducted.” 21 U.S.C. § 355(b)(2) (emphasis
added). Under this section, the relevant investigations are those “relied upon [that
is, chosen] by the applicant.” This language in no way limits which product the
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applicant can rely upon to supply these investigations, much less requires that the
listed drug be the product “most similar” to the test product.
Consistent with the statutory text, FDA’s longstanding position has been that
it is the 505(b)(2) applicant that “should determine which listed drug[s] is most
appropriate for its development program.” JA658; JA68. See also Consolidated
Citizen Petition Response from Janet Woodcock to Katherine M. Sanzo, et al., at
6, Docket Nos. 2001P-0323/CP1 & C5, 2002P-0447/CP1, and 2203P-0408/CP1
(Oct. 14, 2003) (“505(b)(2) Petition Response”) (stating that the 505(b)(2)
applicant may rely on FDA’s finding of safety and effectiveness for “the listed
drug it references”).
FDA’s policy of leaving the choice of the listed drug to the 505(b)(2)
applicant is also the only policy that makes sense given the hybrid nature of this
type of drug approval application. By its very nature, the 505(b)(2) pathway
involves drugs that differ from previously approved drugs in some significant
respect. 505(b)(2) Petition Response at 3 (“a 505(b)(2) application often describes
a drug with substantial differences from the listed drug it references,” such as “a
new dosage form”). As a result, the 505(b)(2) applicant (unlike a manufacturer
seeking approval of an ANDA for a generic copy of a brand product under FDCA
Section 505(j)) cannot rely entirely on the listed drug to supply all of the safety and
effectiveness data it needs for approval. Rather, the applicant relies on some
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combination of (1) preexisting information about the listed drug (such as FDA’s
finding of safety and effectiveness for that product) and (2) the applicant’s own
studies, to prove the test product’s safety and effectiveness. JA654, 659; 505(b)(2)
Petition Response at 3. In these circumstances, it is entirely possible that different
combinations of preexisting information and new data may yield the same ultimate
conclusion: that the proposed drug is safe and effective for its intended use. Thus,
it makes eminent sense for 505(b)(2) applicants to determine in the first instance
the mix of old and new information that it thinks will sustain its burden.
The applicant’s choice of the listed drug will of course inform the quantity
and type of new data needed to fill in the gaps left by the data for the listed drug
relied upon by the 505(b)(2) applicant. As FDA has logically stated: “An applicant
choosing to rely on FDA’s finding of safety and effectiveness for a listed drug very
similar to the [test product] would generally need to submit less additional data to
support the differences between the proposed product and the listed drug for
approval of the 505(b)(2) application.” JA658. See also JA68 (“[T]here is a direct
correlation between the drug the applicant chooses to reference and the applicant’s
burden of proof.”). But as long as the combination of old and new data supports
FDA’s finding of safety and effectiveness, it is, and should be, largely irrelevant to
FDA which listed drug is chosen. See JA70-71 (“[I]n addition to the lack of any
policy on the part of FDA regarding which drug must be referenced in a Section
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505(b)(2) new drug application, there is also no record evidence that clearly
demonstrates that the mere existence of ‘similar’ approved drug products matters
to FDA in practice.”).
Amicus PhRMA supports the “most similar” listed drug test for 505(b)(2)
products by arguing that “there must be consequences that attach to the decision
not to cite a closely-related drug—in particular, the loss of ability to rely on the
findings of safety and efficacy for the omitted drug’s NDA.” PhRMA Br. 28-29.
Putting aside the fact that neither Hikma nor FDA relied on Colcrys in connection
with the Mitigare application and that Mitigare is “closely related” to Col-
Probenecid, the “consequences” for a 505(b)(2) applicant who does not cite the
“closest-related” listed drug are already built into section 505(b)(2): the applicant
must conduct or sponsor more research to fill in the (larger) gaps left by the less-
similar listed drug. This tradeoff is inherent in the 505(b)(2) pathway; there is no
statutory basis or policy reason (other than Appellants’ interest in creating new
advantages for patent holders) to impose a new requirement that the applicant
choose a particular, “most closely-related” listed drug.
Of course, the 505(b)(2) applicant must prove that the information from the
listed drug is “scientifically appropriate and must submit data necessary to support
any aspects of the proposed drug product that represent modifications to the listed
drug(s).” JA659. If FDA reviews a 505(b)(2) application and concludes that the
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sponsor’s new studies do not sufficiently fill in any gaps left by a preexisting FDA
approval (or other preexisting information relied on by the applicant), the sponsor
may well have to reconsider the combination of data in its original application—
including, for example, by choosing a different listed drug or conducting additional
studies. In this case, FDA, exercising expert scientific judgment which is due the
utmost deference from the courts,3 concluded that no such reconsideration was
necessary, and that Hikma’s combination of old and new information supported
approval of Mitigare as safe and effective. But in any event, FDA’s administration
of the FDCA has consistently reflected the flexibility that section 505(b)(2) affords
the applicant, and the agency has not simply mandated the appropriate listed drug.
B. The Court should preserve the intentional distinctions, in Hatch-Waxman and in FDA’s administration of that law, between listeddrugs for 505(b)(2) applications and RLDs for ANDAs.
Takeda’s argument in essence seeks to graft onto section 505(b)(2) a “most
similar” listed drug requirement analogous to the RLD requirement governing
ANDAs under section 505(j) (21 U.S.C. § 355(j)). But the listed drugs under
these two approval pathways are treated differently, with good reason, and
Takeda’s attempts to blur these differences are unavailing.
In the 505(j) context, unlike the 505(b)(2) context, the ANDA applicant
must show that the proposed generic product is in all significant respects the “same
3 Balt. Gas & Elec. Co. v. Nat. Res. Def. Council, Inc., 462 U.S. 87, 103 (1983);Serono Labs., Inc. v. Shalala, 158 F.3d 1313, 1320-21 (D.C. Cir. 1998).
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as” the RLD—i.e., that the two products share, among other things, the same active
ingredient, route of administration, dosage form, strength, and labeling (21 U.S.C.
§ 355(j)(2)(A))—and that the two products are “bioequivalent.” 21 U.S.C. §
355(j)(2)(A)(iv).4 FDA generally chooses the RLD, picking the approved product
to which the duplicate test product must be bioequivalent. See, e.g., 21 C.F.R.
§ 314.94(a)(3) (2014) (“An [ANDA] must refer to a listed drug. Ordinarily, that
listed drug will be the drug product selected by the agency as the reference
standard for conducting bioequivalence testing.”).
Where different products are supposed to be “the same,” and therefore
substitutable for one another, it makes sense for FDA to determine the appropriate
RLD to ensure consistency between and among products. See FDA, Orange Book,
http://tinyurl.com/65wqgnt (“By designating a single reference listed drug as the
standard to which all generic versions must be shown to be bioequivalent, FDA
hopes to avoid possible significant variations among generic drugs and their brand
4 If an ANDA applicant seeks approval of a product that differs in certain respectsfrom the RLD, it must first file a “suitability petition” with FDA. 21 U.S.C.§ 355(j)(2)(C). If FDA finds that additional investigations would be required toestablish the safety or effectiveness of the drug with the different feature, then itwill deny the petition and require the applicant to file a 505(b)(2) petitioninstead. 21 U.S.C. § 355(j)(2)(C)(i). Conversely, if a drug is a duplicate of anapproved drug, its sponsor must file an ANDA under 505(j) and may not proceedunder section 505(b)(2). 21 C.F.R. § 314.101(d)(9) (2014); JA204-05, 207(“[S]ection 505(b)(2) applications should not be submitted for duplicates ofapproved products that are eligible for approval under 505(j)”).
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name counterpart.”).5 But where, as in the 505(b)(2) context, safety and
effectiveness can be established through different combinations of old and new
data, not simply by reference to a single duplicate product, the decision of which
combination to employ, and the related decision of which listed drug to choose,
sensibly rests in the first instance with the applicant.
5 For example, in this very case, FDA determined that all “duplicates” (i.e.,pharmaceutical equivalents) of Colcrys were required to follow the 505(j) pathwayand use Colcrys as the RLD. JA483. Mitigare, which is a capsule, is indisputablynot a “duplicate” of Colcrys, which is a tablet. See 21 C.F.R. § 320.1(c) (2014)(defining “pharmaceutical equivalents” as “drug products in identical dosage formsthat contain identical amounts of the identical active drug ingredient. . . .”)(emphasis added); JA212.
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In sum, FDA has interpreted the section 505(b)(2) provisions with due
regard for its differences from the 505(j) pathway, and this interpretation is
correct.6
II. Elliott’s argument requiring a 505(b)(2) applicant to certify to allpatents covering the same use of the proposed drug wouldfundamentally distort the Hatch-Waxman framework for 505(b)(2)products.
Appellant Elliott goes one step further even than Takeda, arguing that even
if a 505(b)(2) applicant is not required to list a particular drug product as its listed
6 An important related difference between 505(j) products and 505(b)(2) productsis that the first 505(j) applicant referencing a particular RLD that includes a“Paragraph IV” certification challenging one of the RLD’s patents may be eligiblefor 180 days of “generic exclusivity”—i.e., a six-month head start on all othergeneric versions of the RLD (21 U.S.C. § 355(j)(5)(B)(IV))—while 505(b)(2)applicants are ineligible for this exclusivity. Congress included this potentiallylucrative incentive to Hatch-Waxman to encourage patent challenges by ANDAapplicants. Teva Pharms. USA, Inc. v. Sebelius, 595 F.3d 1303, 1305 (D.C. Cir.2010) (“Th[e] promise of initial marketing exclusivity is [] intended to increasecompetition by expediting the availability of generic equivalents.”) (citationsomitted); Hi-Tech Pharmacal Co. v. FDA, 587 F. Supp. 2d 1, 4 (D.D.C. 2008)(“As an incentive for generic pharmaceutical companies to undertake the risk oflitigation and further the statutory purpose of accelerating public access to lower-cost drugs, the first ANDA-applicant that files a paragraph IV certification isentitled to a 180-day period of generic marketing exclusivity.”) (citation omitted).However, section 505(b)(2) products are ineligible for 180-day exclusivity.Instead, Hatch-Waxman gives 505(b)(2) applicants an incentive that rewardsinnovation: three years of exclusivity if they conduct or sponsor new clinicalstudies “essential” to approval. 21 U.S.C. § 355(c)(3)(E)(iii). The unavailability of180-day exclusivity for 505(b)(2) products means that 505(b)(2) applicants haveless of an incentive to challenge brand company patents, and more of an incentiveto choose, as Hikma did, a pathway that avoids any patent certification obligationsbut still provides an expedited path to FDA approval. In other words, Hikma’schoice of development programs in this case is explained by, and appropriategiven, the incentive structure built into Hatch-Waxman by Congress.
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drug, it must certify to any patents that claim the method of using the drug
substance for which 505(b)(2) approval is sought, whether or not that patent was
for the listed drug and whether or not the applicant relied on data relating to
investigations of the drug product covered by the patent. Elliott Br. 16-29.
The district court roundly rejected this interpretation of Hatch-Waxman,
upholding under “Chevron Step One” FDA’s contrary interpretation that a
505(b)(2) applicant need only certify to patents claimed by the drug product relied
on by the applicant. JA74-75 (citing Chevron U.S.A., Inc. v. Nat. Res. Def.
Council, Inc., 467 U.S. 837, 842-43 (1984)). The district court’s analysis was
correct, as was its conclusion that even if Hatch-Waxman is ambiguous on this
issue, FDA’s interpretation is a reasonable interpretation entitled to deference
under “Chevron Step Two.” JA84-85.
GPhA need not restate the extensive textual and structural support for the
district court’s conclusion, except to emphasize that Elliott’s unprecedented
reading of Hatch-Waxman would fundamentally upset the careful balance
Congress sought to achieve between encouraging innovation and expediting
market competition. As the district court explained (JA82), the quid pro quo at the
heart of Hatch-Waxman is that a 505(b)(2) or 505(j) applicant must certify to the
listed drug’s patents (and provide notice of certification to the patent-holder) as a
price for being able to rely on the investigations relating to the listed drug. But if
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an applicant must also certify to use patents for products on which it did not rely, it
is paying a steep price—exposure to resource-draining patent litigation, a 30-
month delay in marketing approval, and greater overall uncertainty regarding its
business—without receiving anything in return. This reading of Hatch-Waxman
simply cannot be squared with the statute’s basic framework and purposes and
would significantly disincentivize use of the 505(b)(2) pathway.
Far from “undermin[ing] the interlocking system of benefits and burdens
Congress built into the Hatch-Waxman Act” (PhRMA Br. 22), the district court’s
decision maintains the Hatch-Waxman system against Elliott’s efforts to distort it.
See JA82 (“[F]rom the standpoint of what Congress intended, if Congress really
meant to tip the carefully-balanced Hatch-Waxman scales so dramatically toward
the protection if innovator’s patent rights, there would be no reason at all for the
statute to so clearly reflect Congress’s interest in achieving that balance at all.”).
PhRMA offers a variant on Elliott’s argument by claiming that an
applicant’s certification obligations under section 505(b)(2) must extend beyond
patents for products that were the subject of the investigations actually “relied
upon” by the applicant, to patents for products that were “essential” to the
505(b)(2) application’s approval. PhRMA Br. 23-24. This reading of the statute
untethers the term “investigations relied upon by the applicant” language from its
plain meaning: to PhRMA, “investigations relied upon by the applicant” includes
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investigations that were not relied on by the applicant. And like Elliott’s statutory
interpretation, PhRMA’s interpretation would expand an applicant’s patent
certification obligations well beyond the scope of the “reliance benefit” received
by the applicant.
III. Hatch-Waxman’s “grand bargain” does not support Appellants’statutory interpretations.
Appellants and their amicus PhRMA repeatedly allude to the “grand
bargain” effected by Hatch-Waxman in support of their statutory interpretations,
which as the district court properly found, would dramatically tilt the Hatch-
Waxman balance of interests in favor of patentholders. JA82.
The particular facts of this case further undercut Appellants’ and PhRMA’s
reliance on the “grand bargain.” First, PhRMA makes much of the billions of
dollars spent by brand companies on the development of innovative new
medicines, arguing that Appellants’ reading of the statute (which would change
how Hatch-Waxman has been interpreted in the 31 years since its enactment) is
necessary to incentivize continued investment. PhRMA Br. 24. But the reality is
that colchicine—singly or in combination with probenecid—has been used for
centuries as a safe and effective treatment of gout; both Takeda and Hikma sold
colchicine products in the past; and Takeda, like Hikma, relied on FDA’s prior
approval of a colchicine combination product under the 505(b)(2) pathway for its
approval. Appellants, having taken advantage of FDA’s prior approval of Col-
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Probenecid through the expedited 505(b)(2) pathway, are now trying to unwind
Hikma’s successful use of that same pathway to regain their monopoly position
and reap monopoly profits for another 30 months. That is not an outcome that
Hatch-Waxman’s “grand bargain” was designed to protect.7
In addition, while Hatch-Waxman’s patent certification process provides a
mechanism to expedite the resolution of patent disputes before FDA approves
generic or 505(b)(2) alternatives, that process is no longer necessary here because
Takeda has already litigated its patent infringement claims against Hikma over
Colcrys patents, and lost. Takeda Pharms. U.S.A., Inc. v. West-Ward Pharm.
Corp., 785 F.3d 625 (Fed. Cir. 2015). Requiring Hikma to follow the certification
procedures at this point would simply give Appellants a windfall by allowing them
to initiate a repeat round of patent litigation, triggering another mandatory 30-
month stay. This relief has no justification in the text, structure, or policies of
Hatch-Waxman.
CONCLUSION
For the foregoing reasons, this Court should affirm the decision below.
7 To the extent that Takeda undertook new drug-drug interaction studies to supportits approval for Colcrys, it has already received a significant Hatch-Waxmanbenefit from that investment, in the form of three-year statutory data exclusivitythat expired in 2013. 21 U.S.C. § 355(c)(3)(E)(iii).
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October 23, 2015 Respectfully submitted,
/s/ Carlos T. AnguloCarlos T. AnguloAndrew N. GoldfarbZuckerman Spaeder LLP1800 M Street, NW, Suite 1000Washington, DC 20036Telephone: (202) [email protected]
Attorneys for Amicus CuriaeGeneric Pharmaceutical Association
USCA Case #15-5021 Document #1579624 Filed: 10/23/2015 Page 25 of 27
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CERTIFICATE OF COMPLIANCE WITH FEDERAL RULE OFAPPELLATE PROCEDURE 32(a)
This brief complies with the type-volume limitation of Federal Rule of
Appellate Procedure 32(a)(7)(B) because this brief contains 4,442 words,
excluding the parts of the brief exempted by Federal Rule of Appellate Procedure
32(a)(7)(B)(iii).
This brief complies with the typeface requirements of Federal Rule of
Appellate Procedure 32(a)(5) and the type style requirements of Federal Rule of
Appellate Procedure 32(a)(6) because this brief has been prepared in a
proportionally spaced typeface using Microsoft Word in 14-point Times New
Roman font.
/s/ Carlos T. AnguloCarlos T. Angulo
USCA Case #15-5021 Document #1579624 Filed: 10/23/2015 Page 26 of 27
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CERTIFICATE OF SERVICE
Pursuant to D.C. Circuit Local Rule 25(c), I hereby certify that on this 23rd
day of October, 2015, I electronically filed the foregoing BRIEF OF AMICUS
CURIAE GENERIC PHARMACEUTICAL ASSOCIATION with the Court by
using the CM/ECF system. All parties to the case have been served through the
CM/ECF system.
/s/ Carlos T. AnguloCarlos T. Angulo
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